The presence of a common mitochondrial DNA variant is associated with fasting insulin levels in Europeans in Auckland

Poulton, Joanna; Bednarz, Amy L.; Scott-Brown, Martin; Thompson, C. F.; Macaulay, Vincent; Simmons, David

doi:10.1046/j.0742-3071.2002.00836.x

Cited by 23 publications

(21 citation statements)

References 13 publications

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“…Consistent with previous studies (Poulton et al 1998(Poulton et al , 2002aCasteels et al 1999), we observed support for a role of T16189C in susceptibility to T2DM-related traits. In offspring, we initially confirmed the association of T16189C with higher fasting insulin and reduced ponderal index (Table 3), as had been reported, and also observed association with reduced birthweight, a trait likely correlated with ponderal index.…”

Section: Discussionsupporting

confidence: 82%

Mitochondrial polymorphisms and susceptibility to type 2 diabetes-related traits in Finns

et al. 2005

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Mitochondria play an integral role in ATP production in cells and are involved in glucose metabolism and insulin secretion, suggesting that variants in the mitochondrial genome may contribute to diabetes susceptibility. In a study of Finnish families ascertained for type 2 diabetes mellitus (T2DM), we genotyped single nucleotide polymorphisms (SNPs) based on phylogenetic networks. These SNPs defined eight major haplogroups and subdivided groups H and U, which are common in Finns. We evaluated association with both diabetes disease status and up to 14 diabetes-related traits for 762 cases, 402 non-diabetic controls, and 465 offspring of genotyped females. Haplogroup J showed a trend toward association with T2DM affected status (OR 1.69, P=0.056) that became slightly more significant after excluding cases with affected fathers (OR 1.77, P=0.045). We also genotyped non-haplogroup-tagging SNPs previously reported to show evidence for association with diabetes or related traits. Our data support previous evidence for association of T16189C with reduced ponderal index at birth and also show evidence for association with reduced birthweight but not with diabetes status. Given the multiple tests performed and the significance levels obtained, this study suggests that mitochondrial genome variants may play at most a modest role in glucose metabolism in the Finnish population. Furthermore, our data do not support a reported maternal inheritance pattern of T2DM but instead show a strong effect of recall bias.

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Section: Discussionsupporting

confidence: 82%

Mitochondrial polymorphisms and susceptibility to type 2 diabetes-related traits in Finns

et al. 2005

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“…A variant at position 16189 has been shown to be associated with elevated fasting insulin concentrations (Poulton et al 1998) and T2D in a population-based case-control study (Poulton et al 2002). Other studies, however, have been unable to replicate this association (Chinnery et al 2005, Mohlke et al 2005, Das et al 2007).…”

Section: Genetic Regulation Of Mitochondria and Associations With T2dmentioning

confidence: 84%

The pathogenetic role of β-cell mitochondria in type 2 diabetes

Fex

Nicholas

Vishnu

et al. 2018

Journal of Endocrinology

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Mitochondrial metabolism is a major determinant of insulin secretion from pancreatic β-cells. Type 2 diabetes evolves when β-cells fail to release appropriate amounts of insulin in response to glucose. This results in hyperglycemia and metabolic dysregulation. Evidence has recently been mounting that mitochondrial dysfunction plays an important role in these processes. Monogenic dysfunction of mitochondria is a rare condition but causes a type 2 diabetes-like syndrome owing to β-cell failure. Here, we describe novel advances in research on mitochondrial dysfunction in the β-cell in type 2 diabetes, with a focus on human studies. Relevant studies in animal and cell models of the disease are described. Transcriptional and translational regulation in mitochondria are particularly emphasized. The role of metabolic enzymes and pathways and their impact on β-cell function in type 2 diabetes pathophysiology are discussed. The role of genetic variation in mitochondrial function leading to type 2 diabetes is highlighted. We argue that alterations in mitochondria may be a culprit in the pathogenetic processes culminating in type 2 diabetes.

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“…The 16,189 variant has been shown to be related to type 2 diabetes and cardiomyopathy [12,13] . Our study also suggests that there is a relationship between this variant and MDSs (odds ratio 2.615, 95% CI 1.012~6.757, P = 0.047).…”

Section: Discussionmentioning

confidence: 99%

“…In previous studies, the frequency of mtDNA variants was shown to be especially higher in the D-loop region. A great deal of mutations in this region were found in leukemia [7] and in many other kinds of tumors [8][9][10][11] , while a single nucleotide polymorphism (SNP) in this region was found to be correlated with some diseases such as diabetes and cardiomyopathy [12,13] . It suggested that the variants in the D-loop region might be related to the pathopoiesis of these diseases.…”

Section: Introductionmentioning

confidence: 99%

Variants of the mitochondrial displacement loop in patients with myelodysplastic syndromes

Cong

et al. 2008

Chin. J. Clin. Oncol.

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OBJECTIVE Some mtDNA mutations have been detected in patients with myelodysplastic syndromes (MDSs). As the noncoding region of mitochondria, the displacement loop (D-loop) region of mtDNA contains important elements for mtDNA replication and transcription. Variants of the D-loop region were found to be related to the cause of many diseases. The aim of our study was to investigate mutations and single nucleotide polymorphisms in the D-loop region of MDS patients. METHODSThe mutations and SNPs in the hypervariable regions of the D-loop were detected by direct sequencing in MDS patients and normal controls. RESULTS Sixty-four SNPs were found in the D-loop region in MDS cases and control group. Among the SNPs, the 16,189 variant (T > C transition) was found to have an increased frequency in the MDS group (P = 0.044). However, no mutations were detected in neither group. CONCLUSIONOur data provide evidence for a highly polymorphic D-loop region in patients with MDS, but do not support the presence of mutations in the mitochondrial D-loop region in MDS cases. The mtDNA T16,189C variant, which may be a functional variant, is associated with increased susceptibility to a MDS.

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The presence of a common mitochondrial DNA variant is associated with fasting insulin levels in Europeans in Auckland

Cited by 23 publications

References 13 publications

Mitochondrial polymorphisms and susceptibility to type 2 diabetes-related traits in Finns

Mitochondrial polymorphisms and susceptibility to type 2 diabetes-related traits in Finns

The pathogenetic role of β-cell mitochondria in type 2 diabetes

Variants of the mitochondrial displacement loop in patients with myelodysplastic syndromes

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